Progesterone Treatment Does Not Prevent Preterm
Birth in Twin Pregnancy

Progesterone therapy does not reduce the chances of preterm birth
in women pregnant with twins, reported researchers in a network
sponsored by the National Institutes of Health.

An earlier study showed progesterone therapy reduced the risk
for preterm birth in another category of high risk pregnant women — those
carrying a single baby who had delivered a single baby prematurely
in the past.

“This study shows that progesterone therapy is not beneficial
for all women at risk for giving birth prematurely,” said Duane
Alexander, M.D., Director of the NICHD, the NIH institute that
supported the research network. “So far, the evidence supports
progesterone therapy as a means to reduce preterm birth only in
women pregnant with a single baby who are at risk for premature
delivery because of a prior preterm birth.”

After the initial study showed progesterone therapy could reduce
the likelihood of preterm birth in women carrying a single baby
and who had previously given birth prematurely, many physicians
began prescribing the therapy for women pregnant with twins and
for other categories of women at risk for preterm birth as well.
In addition to women carrying two or more babies, and those who
have delivered prematurely before, also at risk for preterm delivery
are pregnant women having a shortened cervix (the lower part of
the uterus) and certain infections of the reproductive tract.

The study appears in the August 2, 2007 issue of The New England
Journal of Medicine.

A large team of researchers from the NICHD Maternal-Fetal Medicine
Units Network, led by Dwight J. Rouse, M.D., Professor of Obstetrics
and Gynecology at the University of Alabama at Birmingham School
of Medicine, conducted the study.

In the study, 655 women pregnant with twins were randomly assigned
to receive weekly injections of a placebo or the form of progesterone
known as 17-alpha hydroxyprogesterone caproate (17-OHPC), explained
Catherine Y. Spong, M.D., Branch Chief of NICHD’s Pregnancy and
Perinatology Branch, and the NICHD author of the study.

Progesterone is a female hormone that is produced in large quantities
during pregnancy. Researchers with the Maternal Fetal Medicine
Units Network reported in 2003 that weekly injections of progesterone
reduced the risk of preterm birth by 34 percent among pregnant
women who had given birth prematurely in an earlier pregnancy.

Women in the current study were randomly assigned to groups receiving
weekly injections of either 250 mg of progesterone or a placebo.
The injections started when the women were 16-20 weeks pregnant
and continued until the 35th week of pregnancy or until the woman
gave birth. Women in both groups had similar characteristics such
as age, race, and marital status.

The researchers found that the use of progesterone did not reduce
premature birth in twin pregnancies when compared with the placebo
group: 41.5 percent of women on progesterone treatments delivered
prematurely (before 35 weeks) or experienced fetal loss vs. 37.3
percent of women receiving placebo injections. Fetal loss describes
the loss of the baby because of such factors as stillbirth or miscarriage,
said Dr. Spong.

There was no difference between the two groups in the amount of
time the baby spent in the womb before it was delivered. Progesterone
treatment did not affect the proportion of deliveries before 37
weeks or before 32 or 28 weeks, when compared to the placebo group.

Whether the child was conceived using assisted reproductive methods
or conceived spontaneously did not affect these results, nor did
the type of placentation (whether the babies shared a placenta
or had two separate placentas). The study could not determine whether
progesterone therapy could reduce the chances of preterm birth
in women pregnant with twins who had delivered prematurely in a
previous pregnancy. Fewer than 10 percent of women participating
in the current study had experienced a prior preterm delivery — a
number too small to allow a reliable estimate of the effect of
treatment in this group of women.

Premature infants are often very small and at greater risk for
life-threatening infections, blindness, breathing problems, learning
and developmental disabilities, and cerebral palsy. Premature babies
are also more likely to die from SIDS (sudden infant death syndrome)
than full-term infants. Premature birth is one of the leading causes
of infant death.

Women pregnant with twins are at higher risk for preterm birth
than are other pregnant women, with more than half delivering prematurely,
said Dr. Spong. Over one quarter of all very low birth weight infants
(less than 1500 grams or 3.3 pounds) are the result of a multiple
pregnancy. Multiple pregnancy accounts for one in seven infant
deaths, she said.

Overall, the number of twin births has increased in recent years.
Between 1980 and 2004, the rate of twin birth rose from 18.9 to
32.2 per 1000 live births, the study authors wrote, citing data
from the National Center for Health Statistics.

Dr. Spong added that NIH-funded researchers are testing progesterone
in other groups of women who are at risk for preterm birth, such
as women with shortened cervixes and women pregnant with triplets.

The NICHD sponsors research on development, before and after birth;
maternal, child, and family health; reproductive biology and population
issues; and medical rehabilitation. For more information, visit
the Institute’s Web site at http://www.nichd.nih.gov.

The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.